Targeting the microglia-synapse interface in depression: molecular mechanisms and pharmacological perspectives from traditional Chinese medicine
- 1The First Hospital, Hunan University of Chinese Medicine
- 2Academy of Chinese Medical Sciences, Hunan University of Chinese Medicine
- 3Hunan Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Depressive Diseases
Abstract
Depression is a prevalent neuropsychiatric disorder characterized by impaired synaptic plasticity, disrupted neural circuits, and persistent neuroimmune dysregulation. Increasing evidence indicates that microglia-mediated synaptic pruning, a physiological process essential for neural circuit refinement, becomes abnormally activated under depressive conditions, leading to excessive synaptic elimination and impaired connectivity. Complement-dependent pathways, inflammatory signaling, mitochondrial dysfunction, and alterations in the neural microenvironment contribute to microglial activation and synaptic remodeling. Traditional Chinese Medicine (TCM), with its multi-component and multi-target properties, has shown potential antidepressant effects by regulating neuroinflammation, immune homeostasis, and synaptic plasticity. This review summarizes recent advances in microglia-mediated synaptic pruning in depression and discusses the potential role of TCM interventions in this neuroimmune pathway. Current studies suggest that stress-induced microenvironmental changes promote microglial activation and excessive synaptic engulfment, while TCM formulas, herbal extracts, and bioactive compounds may restore synaptic function by modulating microglial polarization, inflammatory responses, complement signaling, and mitochondrial homeostasis. However, direct evidence demonstrating the regulation of microglia-mediated synaptic pruning by TCM remains limited. Future research integrating single-cell sequencing, advanced imaging, and molecular tracing approaches is required to clarify these mechanisms. Overall, targeting microglial synaptic remodeling provides a promising framework for understanding depression pathogenesis and developing novel TCM-based therapeutic strategies.
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BibTeX
@article{yao2026targeting,
title = {{Targeting the microglia-synapse interface in depression: molecular mechanisms and pharmacological perspectives from traditional Chinese medicine}},
author = {Shu-xia Yao and Zi-yu Xu and Hong-qing Zhao and Dong-fang Deng and Yi Yang and Lin Tang and Hu Tan and Jian Liu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1972377},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1972377/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeting the microglia-synapse interface in depression: molecular mechanisms and pharmacological perspectives from traditional Chinese medicine
AU - Shu-xia Yao
AU - Zi-yu Xu
AU - Hong-qing Zhao
AU - Dong-fang Deng
AU - Yi Yang
AU - Lin Tang
AU - Hu Tan
AU - Jian Liu
PY - 2026
DA - 2026/10/26
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1972377
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1972377/full
AB - Depression is a prevalent neuropsychiatric disorder characterized by impaired synaptic plasticity, disrupted neural circuits, and persistent neuroimmune dysregulation. Increasing evidence indicates that microglia-mediated synaptic pruning, a physiological process essential for neural circuit refinement, becomes abnormally activated under depressive conditions, leading to excessive synaptic elimination and impaired connectivity. Complement-dependent pathways, inflammatory signaling, mitochondrial dysfunction, and alterations in the neural microenvironment contribute to microglial activation and synaptic remodeling. Traditional Chinese Medicine (TCM), with its multi-component and multi-target properties, has shown potential antidepressant effects by regulating neuroinflammation, immune homeostasis, and synaptic plasticity. This review summarizes recent advances in microglia-mediated synaptic pruning in depression and discusses the potential role of TCM interventions in this neuroimmune pathway. Current studies suggest that stress-induced microenvironmental changes promote microglial activation and excessive synaptic engulfment, while TCM formulas, herbal extracts, and bioactive compounds may restore synaptic function by modulating microglial polarization, inflammatory responses, complement signaling, and mitochondrial homeostasis. However, direct evidence demonstrating the regulation of microglia-mediated synaptic pruning by TCM remains limited. Future research integrating single-cell sequencing, advanced imaging, and molecular tracing approaches is required to clarify these mechanisms. Overall, targeting microglial synaptic remodeling provides a promising framework for understanding depression pathogenesis and developing novel TCM-based therapeutic strategies.
SN - 1664-3224
ER -